Compatibility between schistosomes and their snail intermediate hosts is determined in part by the outcome of the interaction of the larval parasite with the host's innate internal defense system (IDS). As in other innate immune systems, the IDS of the vector snail Biomphalaria glabrata is thought to rely on recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). However, both the PAMPs and PRRs important in schistosome-snail interactions are not well understood. The specific aims of the proposed research are to identify one or more specific PAMPs to which the IDS of B. glabrata responds, and then to characterize this response at the transcriptomic level. Recently, a mitotic response to injected crude lipopolysaccharide (LPS) from Escherichia coli has been observed in the hematopoietic amebocyte-producing organ (APO) of schistosome-resistant (but not schistosome- susceptible) B. glabrata, and the pattern of mitotic activity is quite similar to that previously described against injected schistosome extracts. This observation provides an opportunity to identify for the first time a specific PAMP that triggers an immune response in a schistosome-transmitting snail. Should this mitotic activity in fact be directed against LPS, it represents a unique invertebrate response against one of the best characterized microbial PAMPs, and identification of the responsible PAMP(s) may provide insights on recognition of incompatible schistosome larvae by the snail IDS, which presumably evolved largely in response to microbial pathogens long before the recent acquisition of schistosome parasites. The proposed research will test the mitogenic activity of the most likely candidate PAMPs found in crude LPS (i.e., LPS, peptidoglycan, unmethylated CpG-rich DNA), and if activity is associated with LPS itself, then the active component of LPS (i.e., lipid A or the O polysaccharide) will be identified. These studies will utilize histological analysis of cell division in APOs of injected snails. Finally, with the use of microarray analysis, the pattern of gene expression in the APO in response to injection with the active bacterial PAMP will be compared to that previously reported in response to other forms of nonself. PUBLIC HEALTH RELEVANCE: The capacity for a snail to serve as an intermediate host for medically important digenetic trematodes hinges in part on the interaction of the parasite with the host's innate immune system. The proposed research seeks to identify for the first time a specific bacterial molecule that triggers an innate immune response (hematopoiesis) in the schistosome-transmitting snail, Biomphalaria glabrata, and then to characterize the pattern of gene expression in response to this molecule. Results of this study may provide new information on immune recognition of bacterial molecular patterns, as well as insights on the underlying mechanisms of snail-schistosome compatibility.